Chitosan-based glucose-responsive hydrogel with spatiotemporally controlled bactericidal release for diabetic wound...

Diabetic wound healing remains challenging due to the vicious cycle of hyperglycemia-induced bacterial infection, chronic inflammation, and oxidative stress. Here, we developed a glucose-responsive chitosan-gelatin hydrogel (CG) that integrates dynamic microenvironment sensing and on-demand drug release for precise diabetic wound management. Under high-glucose conditions, the phenylboronic acid-diol recognition mechanism triggers the sequential release of dihydromyricetin (DMY) and Cu²⁺ nanoparticles (Cu-DMY NPs). The released Cu-DMY NPs effectively promote macrophage polarization toward the M2 phenotype (10.61 % increase via flow cytometry) by suppressing the NF-κB pathway, thereby reducing pro-inflammatory cytokines. Additionally, in infected microenvironments, the hydrogel exhibits an antibacterial rate of above 80 % against Staphylococcus aureus and Pseudomonas aeruginosa through controlled Cu²⁺ release. In vivo experiments demonstrate that CG-CD hydrogel significantly accelerates diabetic wound closure. This "smart recognition-sequential release-multimodal regulation" strategy provides a novel therapeutic paradigm for diabetic wound healing and advances the design of intelligent wound dressings.